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In spite of being one of the first vitamins to be discovered, the full range of biological activities of Vitamin A remains incomplete. A growing body of evidence has demonstrated an apparent enhancement of carcinogenesis, induced by dietary retinol. Since DNA damage is a well-recognized inducer of carcinogenesis, the aim of this study was to test the possible genotoxic effect of dietary retinol, using...
In the present work, the micronuclei (MN) test was performed in buccal mucosal samples from patients with cancer, with (pre- and post-treatment) and without genotoxic chemotherapy (GC), identified micronucleated cells (MNC) and nuclear abnormalities (binucleated cells (BN), pycnosis (PN), ''broken-egg'' (BE), condensed chromatin (CC), karyorrhexis (KR), and karyolysis (KL)).The objective was to evaluate...
In this study, the genotoxic and cytotoxic potential of lambda-cyhalothrin (LCT), a synthetic pyrethroid insecticide, was investigated in Wistar rat bone-marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. LCT was administrated to adult female albino rats as repeated i.p. doses of 6.12, 3.06, 0.8mg/kg BW for 13 days at 48h intervals. Mitomycin C (MMC)...
Bivalve molluscs, particularly mussels, are sensitive biomarkers of aquatic ecosystem pollution. The tannins, water-soluble plant polyphenols, may play an important role in this environment and, mainly as a consequence of interaction with pollutants, their toxicity may change. We studied three naturally occurring compounds, tannic acid, ellagic acid and gallic acid, for their ability to modulate DNA...
The nephrotoxic and nephrocarcinogenic potential of the haloalkenes is associated with the conjugation of the chemicals to l-glutathione. Subsequent processing of the haloalkene glutathione S-conjugates via the cysteine conjugate β-lyase pathway in the mammalian kidney yields nephrotoxic and mutagenic species. To investigate whether S-conjugates of the model chlorofluoroalkenes 1,1,2-trichloro-3,3,3-trifluoro-1-propene...
In the search for new natural products with anti-oxidant activity, we have combined the cell-free assay based on the scavenging of the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), with a bioassay that detects oxidative mutagens. This bioassay uses a new Escherichia coli tester strain, IC203, specifically sensitive to oxidative stress due to a deficiency in the OxyR function. OxyR is a redox-sensitive...
Transgenic mouse assays have revealed that the mouse intestine, despite its resistance to carcinogenesis, is sensitive to the mutagenicity of some heterocyclic amines (HCAs). Little is known, however, about the level and localization of that sensitivity. We assessed the mutagenicity of four orally administered (20mg/kg per day for 5 days) HCAs-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)...
Perchloroethylene (PERC) is used widely as an industrial dry cleaning solvent and metal degreaser. PERC is an animal carcinogen that produces increased incidence of renal adenomas, adenocarcinomas, mononuclear cell leukemia, and hepatocellular tumors. Oxidative DNA damage and lipid peroxidation were assessed in 38 women with (dry cleaners) or without (launderers) occupational exposure to PERC. PERC...
The effect of the rodent carcinogens acetamide (AC), pyridine (PY) and diethanolamine (DEA) on meiotic chromosome segregation was assessed in 4-day-old Drosophila melanogaster females. After oral treatment with 0.05, 0.1, 0.2 and 0.3% PY; 0.5, 1, 1.5, 2 and 4% AC; or 5, 10, 20, 40 and 80% DEA, the females were mated to 7-day-old males and three 24h broods were obtained to sample cells exposed mainly...
The genotoxicity of endogenously formed N-nitrosamines from secondary amines and sodium nitrite (NaNO 2 ) was evaluated in multiple organs of mice, using comet assay. Groups of four male mice were orally given dimethylamine, proline, and morpholine simultaneously with NaNO 2 . The stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow were sampled 3 and 24h after...
Dimethylarsine and trivalent dimethylated arsenic, metabolites of inorganic arsenics, have received considerable attention in current research because of their biological activities. We attempted to determine the appearance of micronucleated reticulocytes (MNRETs) in mouse peripheral blood following intraperitoneal administration of dimethylarsinous iodide (DMI) and trimethylarsine (TMA), model compounds...
Medaka fish are an established non-mammalian research model for the study of liver carcinogenesis and exposure to environmental pollutants. Studies have emphasized the development of hepatic neoplasms in medaka following exposure to model carcinogens. To date however, little information is known regarding the mechanisms underlying initiation of hepatic tumors in this species. The aim of this study...
Procarbazine [N-isopropyl-α-(2-methylhydrazino)-p-toluamide], a hydrazine derivative, which has been shown to have effective antineoplastic activity, induces cancer in some experimental animals and humans. To clarify a new mechanism for its carcinogenic effect, we examined DNA damage induced by procarbazine in the presence of metal ion, using 32 P-5'-end-labeled DNA fragments obtained...
The genotoxic effects of the anthracycline doxorubicin (DOX) and two of its analogues, epirubicin (EPI) and pirarubicin (THP) were studied using the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. These compounds are classified as topoisomerase II (topo II) poisons, acting by stabilizing a topoisomerase II-cleaved DNA complex. Using the standard version of the SMART...
We have conducted an evaluation of three of the most widely used commercial toxicity prediction programs, Toxicity Prediction by Komputer Assisted Technology (TOPKAT), Deductive Estimation of Risk from Existing Knowledge (DEREK) for Windows (DfW) and CASETOX. The three programs were evaluated for their ability to predict Ames test mutagenicity using 520 proprietary drug candidate (Test set 1) and...
Apomorphine (APO) is considered to be a classical mixed type dopamine D 1 and D 2 receptor agonist. It has been used in the therapy of Parkinson's disease and, more recently, for the treatment of erectile dysfunction. Like other catechols (e.g. dopamine), APO easily autoxidizes, producing quinone and semiquinone derivatives that may lead to the formation of reactive oxygen species...
The purpose of this study was to assess DNA damage of tumor-associated lymphocytes (TALs) in malignant pleural effusion (MPE), the total antioxidant capacity (TAC) of plasma and MPE from patients with carcinoma, and DNA repair effect of melatonin. TAC of plasma was measured in 28 cancer patients with MPE and in 33 healthy persons, and also TAC of MPE supernatant was measured in these patients. DNA...
Twenty-five commercial pet foods were analyzed for mutagenic activity using the Ames/Salmonella test with strain TA98 and added metabolic activation. All but one gave a positive mutagenic response. Fourteen of these samples were analyzed for heterocyclic amine mutagens/carcinogens and all but one contained 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 10 of 14 contained 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine...
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